动脉粥样硬化血栓疾病的炎症和发病机制PPT课件
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Gu L et al. Mol Cell 1998;2:275-281.
Reduced Lipid Deposition in MCP-1– Deficient Atherosclerotic Mice
LDL-R –/– MCP-1 +/+
LDL-R –/– MCP-1 –/–
Gu L et al. Mol Cell 1998;2:275-281.
M-CSF Expression in Atheroma
Intimal M-CSF
in Atheroma
M-CSF Promotes Atherogenesis
Reduced Lipid Deposition in MCP-1– Deficient Atherosclerotic Mice
30
Oil Red Staining % Aortic Surface Stained
25
20
15
10
**
*
5
0
+/+ -/-
+/+ -/-
Time on Diet:
12 – 14 weeks
Localizes in human and experimental atheroma
Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low-density lipoprotein receptor– deficient mice
Intrinsic Vascular Wall Cells: Endothelium Smooth Muscle Cells Inflammatory Cells: Macrophages T Lymphocytes Mast Cells
Cell Types in the Human Atheroma
Macrophage Functions in Atherogenesis
Division
Macrophage Colony-Stimulating Factor (M-CSF)
A potent monocyte activator and comitogen
Produced by endothelial and smooth muscle cells
Localizes in human and experimental atheroma
Augmented M-CSF gene expression in human and experimental atherogenesis
Rosenfeld ME et al. Am J Pathol 1992;140:291-300. Clinton SK et al. Am J Pathol 1992;140:301-316.
Macrophage Functions in Atherogenesis
Penetration
Monocyte Chemoattractant Protein 1 (MCP-1)
A potent mononuclear cell chemoattractant
Produced by endothelial and smooth muscle cells
Monocyte/ Macrophage
Intima
Tunica Media
Endothelium
T-lymphocytes Smooth muscle cells
Schematic Time Course of Human Atherogenesis
Ischemic Heart Disease
Cerebrovascular Disease
Expressed by microvessels of the mature atheroma
An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium
Li H et al. Arterioscler Thromb 1993;13:197-204.
VCAM-1 Expression in Rabbit Aorta
3 weeks on atherogenic diet
Li H et al. Arterioscler Thromb 1993;13:197-204.
Mono
T
B
PMN
Vascular Cell Adhesion Molecule 1 (VCAM-1)
Binds monocytes and lymphocytes - Cells found in atheroma
Expressed by endothelium over nascent fatty streaks
Lesion initiation
Peripheral Vascular DΒιβλιοθήκη Baidusease
No symptoms
+ Symptoms
Symptoms
Time (y)
Macrophage Functions in Atherogenesis
Attachment
Leukocyte–Endothelial Adhesion Molecules
Inflammation and the Pathogenesis of Atherothrombotic Disease
Peter Libby, M.D.
Atheroma are not merely filled with lipid, but contain cells whose functions critically influence atherogenesis:
20 – 25 weeks
Gu L et al. Mol Cell 1998;2:275-281.
*P = 0.001 compared to +/+ **p = 0.005 compared to +/+
Macrophage Functions in Atherogenesis
Activation
Reduced Lipid Deposition in MCP-1– Deficient Atherosclerotic Mice
LDL-R –/– MCP-1 +/+
LDL-R –/– MCP-1 –/–
Gu L et al. Mol Cell 1998;2:275-281.
M-CSF Expression in Atheroma
Intimal M-CSF
in Atheroma
M-CSF Promotes Atherogenesis
Reduced Lipid Deposition in MCP-1– Deficient Atherosclerotic Mice
30
Oil Red Staining % Aortic Surface Stained
25
20
15
10
**
*
5
0
+/+ -/-
+/+ -/-
Time on Diet:
12 – 14 weeks
Localizes in human and experimental atheroma
Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low-density lipoprotein receptor– deficient mice
Intrinsic Vascular Wall Cells: Endothelium Smooth Muscle Cells Inflammatory Cells: Macrophages T Lymphocytes Mast Cells
Cell Types in the Human Atheroma
Macrophage Functions in Atherogenesis
Division
Macrophage Colony-Stimulating Factor (M-CSF)
A potent monocyte activator and comitogen
Produced by endothelial and smooth muscle cells
Localizes in human and experimental atheroma
Augmented M-CSF gene expression in human and experimental atherogenesis
Rosenfeld ME et al. Am J Pathol 1992;140:291-300. Clinton SK et al. Am J Pathol 1992;140:301-316.
Macrophage Functions in Atherogenesis
Penetration
Monocyte Chemoattractant Protein 1 (MCP-1)
A potent mononuclear cell chemoattractant
Produced by endothelial and smooth muscle cells
Monocyte/ Macrophage
Intima
Tunica Media
Endothelium
T-lymphocytes Smooth muscle cells
Schematic Time Course of Human Atherogenesis
Ischemic Heart Disease
Cerebrovascular Disease
Expressed by microvessels of the mature atheroma
An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium
Li H et al. Arterioscler Thromb 1993;13:197-204.
VCAM-1 Expression in Rabbit Aorta
3 weeks on atherogenic diet
Li H et al. Arterioscler Thromb 1993;13:197-204.
Mono
T
B
PMN
Vascular Cell Adhesion Molecule 1 (VCAM-1)
Binds monocytes and lymphocytes - Cells found in atheroma
Expressed by endothelium over nascent fatty streaks
Lesion initiation
Peripheral Vascular DΒιβλιοθήκη Baidusease
No symptoms
+ Symptoms
Symptoms
Time (y)
Macrophage Functions in Atherogenesis
Attachment
Leukocyte–Endothelial Adhesion Molecules
Inflammation and the Pathogenesis of Atherothrombotic Disease
Peter Libby, M.D.
Atheroma are not merely filled with lipid, but contain cells whose functions critically influence atherogenesis:
20 – 25 weeks
Gu L et al. Mol Cell 1998;2:275-281.
*P = 0.001 compared to +/+ **p = 0.005 compared to +/+
Macrophage Functions in Atherogenesis
Activation